The effects of cyclazocine and hydromorphone on spontaneous and laboratory cigarette smoking were compared in a double-blind, placebo-controlled, crossover study. Participants (seven men, one woman) received oral doses of placebo, cyclazocine (0.2, 0.4, and 0.8 mg) and hydromorphone (5 and 15 mg) in a randomized order on experimental days. Spontaneous smoking was recorded during two intervals on the experimental days: a 3-h period 5-8 h after drug administration (Interval 1), and the rest of the day (Interval 2). Measures of smoking topography and subjective and physiologic effects of a single cigarette were obtained on the experimental days. Neither hydromorphone nor cyclazocine significantly changed spontaneous smoking when compared to the placebo condition; however, compared to hydromorphone (5 mg), cyclazocine (0.4 and 0.8 mg) decreased spontaneous smoking during Interval 1. Hydromorphone (5 and 15 mg) and cyclazocine (0.4 and 0.8 mg) diminished smoking-induced increases in heart rate. Compared to the placebo condition, cyclazocine (0.2 and 0.4 mg) reduced exhaled carbon monoxide (CO) boost, a measure of smoke exposure. Further studies of the effects of kappa opioid agonists on smoking behavior may lead to a better understanding of the role of opiates in smoking behavior.
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http://dx.doi.org/10.1016/j.pbb.2004.01.022 | DOI Listing |
BMC Pharmacol
January 2006
Department of Pharmacology, Molecular Research Institute, Mountain View, CA 94043, USA.
Background: The aim of the present study was to describe the activity of a set of opioid drugs, including partial agonists, in a human embryonic kidney cell system stably expressing only the mouse kappa-opioid receptors. Receptor activation was assessed by measuring the inhibition of cyclic adenosine mono phosphate (cAMP) production stimulated by 5 microM forskolin. Intrinsic activities and potencies of these ligands were determined relative to the endogenous ligand dynorphin and the kappa agonist with the highest intrinsic activity that was identified in this study, fentanyl.
View Article and Find Full Text PDFPharmacol Biochem Behav
April 2004
National Institute on Drug Abuse (NIDA), Intramural Research Program, Clinical Pharmacology and Therapeutics Branch, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
The effects of cyclazocine and hydromorphone on spontaneous and laboratory cigarette smoking were compared in a double-blind, placebo-controlled, crossover study. Participants (seven men, one woman) received oral doses of placebo, cyclazocine (0.2, 0.
View Article and Find Full Text PDFBehav Pharmacol
March 2004
National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA.
Kappa-opioid agonists produce neurobiological and behavioral effects opposite to those of cocaine and may be useful for the treatment of cocaine dependence. To evaluate the kappa- and mu-agonist effects of cyclazocine and to test whether cyclazocine pretreatment would attenuate the effects of cocaine, healthy, male and female, experienced opiate and cocaine users (n = 13) were enrolled in a two-phase study. In Phase 1, placebo, cyclazocine (0.
View Article and Find Full Text PDFBMC Pharmacol
January 2003
Department of Pharmacology, Molecular Research Institute, Mountain View, CA 94043, U.S.A.
Background: The aim of the present study was to describe the activity of a set of opioid drugs, including partial agonists, in a cell system expressing only mu opioid receptors. Receptor activation was assessed by measuring the inhibition of forskolin-stimulated cyclic adenosine mono phosphate (cAMP) production. Efficacies and potencies of these ligands were determined relative to the endogenous ligand beta-endorphin and the common mu agonist, morphine.
View Article and Find Full Text PDFBMC Neurosci
November 2002
Molecular Research Institute, Mountain View, CA 94043, USA.
Background: The aim of the present study was to characterize the activation profiles of 15 opioid ligands in transfected human embryonic kidney cells expressing only delta opioid receptors. Activation profiles of most of these ligands at delta opioid receptors had not been previously characterized in vitro. Receptor activation was assessed by measuring the inhibition of forskolin-stimulated cAMP production.
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